Ultrafine/nanoparticles (NPs) from many environmental sources, including those produced by the exploding field of nanotechnology, can occur in occupational and environmental settings and present humans with both exposures and toxicities. Even more of an issue is the expanding field of nanomedicine. Current research has not had the pregnant woman or fetus as a major focus. We plan to examine whether NPs can cross into the fetus through the human placenta in vitro. Because of their small size and large surface area per unit area, the propensity of NPs to interact biologically is high. Inhaled NPs exit the respiratory tract into circulation with distribution to extrapulmonary tissues. When NPs enter the blood stream they become coated with serum proteins, which may influence the manner in which they are recognized by these tissues. Two proteins in particular, IgG and albumin, are selectively recognized and either transported (IgG) or catabolized (albumin) by the placenta. HYPOTHESIS: In the human, NPs in maternal blood can cross the placenta and enter into fetal circulation, and this transfer of NPs is dependent on the protein surface coating and size of the NPs. SPECIFIC AIM 1: Determine the ability of NPs to accumulate and transfer into the fetal circuit by the perfused human placenta in vitro using 5 nm gold (Au) particles coated with human F105 IgG or serum albumin, SPECIFIC AIM 2: Determine if larger NPs transit from the maternal to fetal circuits under perfusion conditions using similarly coated 50 nm Au NPs. SPECIFIC AIM 3: Determine if exposure to NPs induces dysfunction in the human placenta using dynamic functional, morphologic, biochemical and endocrine assessments. These studies will establish whether the human placenta will a. accumulate Au NPs according to size and protein coating, b. transfer these Au NPs selectively from maternal to fetal circulation, and c. become acutely intoxicated due to interaction with any of these NPs formulations. A major objective of these experiments is to initiate development of a model that will help assess the developmental effects of nanomaterials in the maternal circulation. FUTURE DIRECTIONS: Using these model Au NPs, results from this project will be the basis for subsequent research objectives using other types of NPs, e.g., partially soluble and biodegradable NPs and NPs with varying surface charge and size to identify a) the mechanisms of placental transfer of NPs and the dependence not only on size and protein coating, but also on charge, solubility, and other physicochemical characteristics, and b) the fate, effects, and underlying mechanisms of NPs in the human placenta at different stages of gestation. This work will identify the potential for the embryo/fetus to be directly exposed to different environmental NPs, and for the placenta to be affected. PUBLIC HEALTH RELEVANCE: This study will determine if nanoparticles of different sizes and protein coatings will cross the placenta and enter into the fetal circulation utilizing a dually perfused human placenta lobule in vitro.